The present disclosure describes improvements to the manner of using and operating a small coin-sized electroacupuncture (EA) stimulator of the type described in the related patent applications referenced above, or equivalent small self-contained stimulators, adapted for implantation at selected tissue, nerve or acupoint target locations. More particularly, the present disclosure relates to a method of formulating or providing a stimulation paradigm for use within an implantable EA device that improves blood pressure (BP) “dipping” of a patient who uses the EA device for the treatment of hypertension or of a nondipping or reverse dipping condition.
Blood pressure “dipping” refers to changes that occur in a patient's blood pressure during the nighttime. Blood pressure, or “BP”, in healthy individuals typically falls by about 15% during the nighttime or during sleep. Where blood pressure falls by less than 10% during the night, it is called nondipping, or reverse dipping if it rises. The term “nondipping” commonly includes reverse dipping.
Independent of the degree of hypertension, nondipping and reverse dipping have been identified as a strong risk factor for cardiovascular target organ damage. In an Irish study of over 5000 untreated hypertensive patients, the relative hazard ratio for each 10 mm Hg increase in systolic blood pressure (SBP) was 1.12 (1.06-2.28) for daytime and 1.21 (1.15-1.27) for nighttime blood pressure. See, e.g., Dolan, “Superiority of Ambulatory Over Clinic Blood Pressure Measurement in Predicting Mortality—The Dublin Outcome Study,” Hypertension 2005, 46:156-161: originally published online Jun. 6, 2005.
Relatedly, a significant increase in blood pressure in the morning hours appears to be associated with worse cardiovascular outcomes. See, Kario K, Pickering TG, Umeda Y, et al. “Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study.” Circulation. 2003; 107(1):1401-1406.
Nondipping or reverse dipping occurs in about 1 in 3 hypertensive people. See, e.g., Burnier M, Coltamai L, Maillard M, Bochud M, “Renal sodium handling and nighttime blood pressure,” Semin Nephrol. 2007: 27(5):565-571; Bankir L, Bochud M, Maillard M, Bovet P, Gabriel A, Burnier M, “Nighttime blood pressure and nocturnal dipping are associated with daytime urinary sodium excretion in African subject,” Hypertension 2008, 51(4):891-898.
In a large cohort of 7,458 patients from Europe, Asia, and South America, nighttime blood pressure, adjusted for daytime pressure was found to predict total cardiovascular, and noncardiovascular mortality, but daytime blood pressure, adjusted for nighttime blood pressure, only predicted noncardiovascular mortality. Thus, nighttime blood pressure is an important predictor of cardiovascular and other mortality—even more important than daytime blood pressure. See, Boggia, J, Li Y, Thijs L, et al., “Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study,” Lancet. 2007; 370 (9594): 1219-1229.
Recently, chronotherapeutics have arisen as a way to improve outcomes in consideration of the danger of nondipping or reverse dipping. Chronotherapeutics means the purposeful timing of medications to reduce both nondipping and quick morning rises in blood pressure. Antihypertensives are prescribed at nighttime for this improvement. Research by a group led by Hermida in Spain has shown that bedtime, as opposed to morning, dosing of various classes of antihypertensive medications leads to improvements in some key blood pressure parameters. Bedtime administration of telmisartan, for example, was shown to better reduce the mean nocturnal blood pressure than morning administration of the drug. Furthermore, telmisartan at night significantly reduced nondipping from 34% to 8% of patients as opposed to the failure to reduce nondipping when administered at morning. Results have been similar in the nighttime administration of ARBs, ACEi, CCBs, and alpha-blockers.
The present application does not deal with the administration of drugs to control hypertension. Rather, the application deals with applying electroacupuncture (EA) stimulation pulses to specific tissue locations for the purpose of treating hypertension, or other physiological maladies. But, as is discussed hereinafter, there is a need to know when such EA stimulation pulses should be applied to the specific tissue locations. The present application addresses that and other needs.
In accordance with the teachings of the applications referenced above, a self-contained, coin-sized stimulator may be implanted in a patient at or near a specified acupoint(s) in order to favorably treat a condition or disease of a patient. The coin-sized stimulator advantageously applies electrical stimulation pulses at very low levels and duty cycles in accordance with specified stimulation regimens through electrodes that form an integral part of the housing of the stimulator. A small battery inside of the coin-sized stimulator provides sufficient energy for the stimulator to carry out its specified stimulation regimen over a period of several months or years. Thus, the coin-sized stimulator, once implanted, provides an unobtrusive, needleless, long-lasting, elegant and effective mechanism for treating certain conditions and diseases that have long been treated by acupuncture or electroacupuncture.
It is noted that electroacupuncture, or EA, has long been used by certain acupuncturists as an alternative to classical acupuncture. In classical acupuncture treatment, needles are inserted into the patient's body at specified acupoints located throughout the human body. The location of the acupoints on the human body is well documented, see, e.g., WHO STANDARD ACUPUNCTURE POINT LOCATIONS IN THE WESTERN PACIFIC REGION, published by the World Health Organization (WHO), Western Pacific Region, 2008 (updated and reprinted 2009), ISBN 978 92 9061 248 7 (hereafter “WHO Standard Acupuncture Point Locations 2008”). The reference book, “WHO Standard Acupuncture Point Locations 2008” is incorporated herein by reference. It is significant that the location of the acupoints shown, e.g., in WHO Standard Acupuncture Point Locations 2008, has been determined based on over 2500 years of practical experience.
Despite the well-documented location of acupoints, it is noted that references to these acupoints in the literature have not always been consistent with respect to the format of the letter/number/name combination used to identify a particular acupoint. For example, some acupoints are identified by a name only, e.g., Tongi. The same acupoint may be identified by others by the name followed with a letter/number combination placed in parenthesis, e.g., Tongi (HT5). Other citations place the letter/number combination first, followed by the name, e.g., HT5 (Tongi). The first letter typically refers to a body organ, or other tissue location associated with, or affected by, that acupoint. However, usually only the letter is used in referring to the acupoint, but not always.
For purposes of this patent application, unless specifically stated otherwise, all references to acupoints that use the same name, or the same first letter and the same number, and regardless of slight differences in second letters and formatting, are intended to refer to the same acupoint. Thus, for example, the acupoint Neiguan is the same acupoint as Neiguan (P6), which is the same acupoint as Neiguan (PC6), which is the same acupoint as Neiguan (PC-6), which is the same acupoint as Neiguan (Pe-6), which is the same acupoint as P6, or PC6, or PC-6 or Pe 6.
In classical acupuncture treatment, once needles are inserted at a desired acupoint location(s), the needles are then mechanically modulated for a short treatment time, e.g., 30 minutes or less. The needles are then removed until the patient's next visit to the acupuncturist, e.g., in 1-4 weeks or longer, when the process is repeated. Over several visits, the patient's condition or disease is effectively treated, offering the patient needed relief and improved health.
In electroacupuncture treatment as described and practiced in the prior art, needles are inserted at specified acupoints, as in classical acupuncture treatment, but the needles, once inserted, are then connected to a source of electrical radio frequency (RF) energy, and electrical stimulation signals, at a specified frequency and intensity level, are then applied to acupoint(s), thereby also providing the patient with a measure of needed and desired treatment for his or her condition or disease.
One important use of the implantable EA devices described in the patent applications referenced above is for the treatment of hypertension. However, in order to maximize the efficacy of treating hypertension using an implantable EA device, there is a need for a preferred technique for configuring the stimulation paradigm provided by the EA device. Included in such stimulation paradigm, or stimulation regimen, is a preferred timing (time of day) for when such EA stimulation pulses should be applied to the specified tissue location. The present application addresses that need.